Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life.

OBJECTIVE: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. METHODS: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t = -0.553, df = 542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATPmax]; t = 0.804, df = 553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D ≥16) at follow-up (ΔATPmax: odds ratio = 2.63, χ2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ2 = 5.79, df =1; p = 0.016). CONCLUSION: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with LLD.

Vitrectomy, Inner Limiting Membrane Peel, and Gas Tamponade in the Management of Traumatic Paediatric Macular Holes: A Case Series of 13 Patients.

PURPOSE: To review the outcomes of pars plana vitrectomy, internal limiting membrane (ILM) peel, and gas tamponade in the management of traumatic paediatric macular holes. METHODS: Retrospective case series of children undergoing vitrectomy, ILM peel, and gas tamponade for traumatic macular hole between March 2007 and July 2014. Main outcome measures were postoperative visual acuity at 3 and 12 months, anatomic closure rate, and surgical complications. RESULTS: Anatomic macular hole closure was achieved in 12 (92.3%) of 13 cases. Mean preoperative logMAR visual acuity was 0.91 (95% CI 0.65-1.17) with improvement postoperatively to 0.54 (95% CI 0.43-0.64) at 3 months (p = 0.002) and 0.50 (95% CI 0.39-0.60) at 12 months (p = 0.002). There were no perioperative complications. CONCLUSION: Pars plana vitrectomy and ILM peel is an effective management option for paediatric macular holes.

Circadian Rhythms in Fear Extinction Recall Depend on the Time of Day of Extinction Recall, Not the Time of Day of Extinction Learning.

The recall of conditioned fear extinction exhibits a circadian rhythm in humans and rodents, with optimal extinction recall occurring during the early active phase. However, it remains unclear whether this rhythm depends on the circadian modulation of mechanisms supporting memory consolidation versus memory maintenance and retrieval. Here, adult male rats underwent conditioned fear extinction at one of four times throughout the day and then, starting 24 h after extinction, were repeatedly tested for extinction recall over the next 24 h. Rats undergoing extinction learning during the early active phase tended toward accelerated extinction learning compared with rats in other groups, pointing to rhythms in mechanisms that support extinction memory encoding. The next day, the strength of extinction recall followed a 24-h cycle that depended not on the time of day of extinction learning but, instead, on the time of day of extinction recall. This latter finding indicates a rhythm in mechanisms supporting extinction memory maintenance and/or retrieval. Subsequent testing for fear relapse in the conditioning context suggested reduced fear in rats tested during the early active phase. These results lay the groundwork for mechanistic investigations of circadian rhythms in fear extinction memory.

Patient generated aerosol in the context of ophthalmic surgery.

OBJECTIVE: To assess the patterns of patient generated aerosol in the context of ophthalmic surgery and ophthalmic examinations. To inform medical teams regarding potential hazards and suggest mitigating measures. METHODS: Qualitatively, real-time time videography assessed exhalation patterns from simulated patients under different clinical scenarios using propylene glycol from an e-cigarette. Quantitatively, high-speed Schlieren imaging was performed to enable high resolution recordings analysable by MATLAB technical computing software. RESULTS: Without a face mask, the standard prior to COVID 19, vapour was observed exiting through the opening in the drape over the surgical field. The amount of vapour increased when a surgical mask was worn. With a taped face mask, the amount of vapour decreased and with inclusion of a continuous suction device, the least amount of vapour was seen. These results were equivocal when the patient was supine or sitting upright. High-speed Schlieren imaging corroborated these findings and in addition showed substantial increase in airflow egress during coughing and with ill-fitting face masks. CONCLUSION: Advising patients to wear a surgical mask at the time of ophthalmic interventions potentially contaminants the ocular field with patient generated aerosol risking endophthalmitis. Surgeon safety can be maintained with personal protective equipment to mitigate the increased egress of vapour from the surgical drape and taping, with or without suction is advisable, whilst meticulous hygiene around lenses is required at the time of slit lamp examination.

Implementing electronic medication management at an Australian teaching hospital.

We describe the implementation of an electronic medication management system (eMMS) in an Australian teaching hospital, to inform future similar exercises. The success of eMMS implementation depends on: a positive workplace culture (leadership, teamwork and clinician ownership); acceptance of the major impact on work practices by all staff; timely system response to user feedback; training and support for clinicians; a usable system; adequate decision support.

Groove pancreatitis. A mini-series report and review of the literature.

CONTEXT: Groove pancreatitis is a rare condition characterized by fibrotic inflammation affecting the groove anatomical area between the head of the pancreas, the duodenum and the common bile duct. OBJECTIVES: We report a miniseries of five cases treated surgically in our centre over a period of four years. A review of the literature is also discussed. METHODS: Patients undergoing pancreaticoduodenectomy over a four-year period were retrospectively reviewed. Patients with a confirmed histological diagnosis of groove pancreatitis were assessed under the headings; patient demographics, presenting symptoms, radiological and histological findings. RESULTS: One-hundred and 60 pancreaticoduodenectomies were performed. Thirty-nine cases demonstrated benign disease and within this, five cases (3.1% of total series; 12.8% of benign cases) were groove pancreatitis. All patients presented with abdominal pain and weight loss, and the majority consumed excess alcohol and were smokers. Radiological findings (CT/MRCP/EUS) revealed duodenal wall thickening in all cases, abnormalities at the head of pancreas and bile duct dilation in four, and cystic changes in the duodenal wall and pancreatic duct dilation in three cases. Groove fibrosis, Brunner's gland hyperplasia and cystic changes in duodenal wall were present in all cases on histological review. All patients reported significant improvement in quality of life at 12 months after surgery. CONCLUSION: Groove pancreatitis can present in a similar fashion to head of pancreas cancer and chronic pancreatitis. For this reason it is paramount for clinicians to be aware of groove pancreatitis, as this can lead to the correct diagnosis and management of this unique disease.

Intraductal papillary mucinous neoplasm (IPMN) and chronic pancreatitis: overlapping pathological entities? Two case reports.

CONTEXT: Intraductal papillary mucinous neoplasms (IPMNs) are a recently classified pancreatic neoplasm with an increasing incidence. IPMN is often misdiagnosed as chronic pancreatitis because of symptoms of relapsing abdominal pain, pancreatitis, and steatorrhea and imaging findings of a dilated pancreatic duct of cystic lesions that are frequently confused with pseudocysts. Early recognition of IPMN allows for prompt surgical resection before malignant transformation. CASE REPORTS: We report two cases of patients with long histories of chronic pancreatitis (more than 15 years) that went on to develop IPMN. Both patients presented with symptoms of abdominal pain, nausea, steatorrhoea and eventually weight loss. Biochemical and radiological findings were suggestive of chronic pancreatitis although no clear causes for this were identified. Both patients were followed up with multiple repeat scans with no reported sinister findings. Many years after the initial diagnosis of chronic pancreatitis, radiological investigations identified pathological changes suggestive of neoplastic development and histology confirmed IPMN. CONCLUSIONS: The cases demonstrate the ongoing challenges in diagnosing and managing IPMN effectively; highlights the important aspects of epidemiology in differentiating chronic pancreatitis and IPMN; continues the discussion surrounding the relationship between IPMN and chronic pancreatitis.

Spontaneous intraperitoneal rupture of pyonephrosis in a patient with unknown kidney carcinosarcoma: a case report.

Seventeen cases of peritonitis due to rupture of a pyonephrosis have been reported. The majority of these cases occur secondary to renal stones. Only two cases of ruptured pyonephrosis with concurrent kidney neoplasm have been described and only one of these presented as an acute peritonitis. In this presentation we discuss an unusual case of a 68 year old man with a chronic history of bilateral nephrolithiasis and recent pyonephrosis. He presented acutely with peritonitis and was later found to have a carcinosarcoma of the kidney. The case highlights the importance of recognizing the possibility of underling renal carcinoma in patients presenting with a ruptured pyonephrosis and discuss steps to avoid this serious complication.

Contribution of Intramyocellular Lipids to Decreased Computed Tomography Muscle Density With Age.

Skeletal muscle density, as determined by computed tomography (CT), has been shown to decline with age, resulting in increased frailty and morbidity. However, the mechanism underlying this decrease in muscle density remains elusive. We sought to investigate the role of intramyocellular lipid (IMCL) accumulation in the age-related decline in muscle density. Muscle density was measured using computerized tomography (CT), and IMCL content was quantified using in vivo proton magnetic resonance spectroscopy (1H-MRS). The study population consisted of 314 healthy participants (142 men, 32-98 years) of the Baltimore Longitudinal Study of Aging (BLSA). In addition to IMCL quantification, obesity-related covariates were measured, including body mass index (BMI), waist circumference, and circulating triglyceride concentration. Higher IMCL concentrations were significantly correlated with lower muscle density in older individuals, independent of age, sex, race, and the obesity-associated covariates (p < 0.01). Lower muscle density was also significantly associated with greater age-adjusted IMCL, a variable we constructed using LOESS regression (p < 0.05). Our results suggest that the accumulation of IMCL may be associated with a decrease in muscle density. This may serve to define a potential therapeutic target for treatment of age-associated decreased muscle function.

GIST suture-line recurrence at a gastrojejunal anastomosis 8 years after gastrectomy: can GIST ever be described as truly benign? A case report.

We present the case of a 71 year old man with recurrence of a Gastro Intestinal Stromal Tumour (GIST) at the gastrojejunal anastomosis eight years following partial gastrectomy for a very small primary gastric GIST. He presented acutely on both occasions with haemodynamic shock secondary to massive haematemesis. During his initial presentation in 2001, an emergency laparotomy was performed, demonstrating a pre-pyloric ulcerative lesion. The histopathology was in keeping with a diagnosis of a gastric GIST with a <2 cm tumour, with <5 mitosis per 50/HPF, no signs of necrosis and invasion limited to the mucosa. Eight years later the same patient presented with a similar clinical picture of haemodynamic instability secondary to haematemesis. Emergency endoscopy showed an irregularly shaped elevated lesion on the gastrojejunostomy line suggestive of recurrence. He subsequently underwent completion gastrectomy and the histology revealed a 0.8 cm GIST tumour composed of spindle cells with <5 mitosis per 50/HPF, tumor invasion into the submucosa and positive expression of c-kit and SMA. The patient remains recurrence free 18 months post surgery. The literature suggests that tumour size, mitotic rate and tumour site are the most important predictive factors of recurrence. Additional features such as the presence of necrosis, local tumour invasion and positive resection margins, can also influence recurrence rates. In this case the lesion was a gastric GIST, very small (<2 cm), had low proliferation rate (<5 mitosis/HPF), lacked necrosis and was limited to the mucosa. Recurrence of such a primary GIST at the anastomotic line, eight years after initial resection has never been demonstrated among review of several thousand primary GISTs. This case highlights how even the most innocent GISTs can never be described as truly benign.

Retinal detachment in retinitis pigmentosa.

OBJECTIVE: Retinitis pigmentosa-related retinal detachment (RPRD) is rare, and the full spectrum of retinal complications is not well defined. To describe the types of retinal detachment in patients with retinitis pigmentosa and the surgical outcomes of RPRD. METHODS: This is a non-comparative, retrospective case series. An electronic database search was performed using Moorfields OpenEyes electronic health records. We identified 90 patients with RPRD between January 2000 and August 2017. Main outcome and measures are visual acuity (VA), surgical outcomes and classification of RPRD. RESULTS: Of the 90 patients/detachments, 61 (67.8%) were rhegmatogenous retinal detachment (RRD), 19 (21.1%) were exudative, 3 (3.3%) were tractional retinal detachment (TRD) and 7 (7.8%) had combined. 37.5% (9/24) of patients with exudative retinal detachment were treated with either cryotherapy or laser, and one patient underwent vitrectomy for vitreous haemorrhage. 56/90 patients underwent surgical intervention. Nine patients presented late and were deemed inoperable (two exudative and seven RRD). Of the RRD patients with full operative record, the primary attachment rate was 76.2% (16/21) and final reattachment rate was 85.7% (18/21) over a mean 15.4-year follow-up period. Mean VA for RRD surgery improved from 6/190 (1.51 logMAR) to 6/120 (1.31 logMAR) (p=0.194). In the TRD group, the mean VA was 6/300 (1.66 logMAR) at baseline and improved after surgery to 6/48 (0.90 logMAR) (p=0.421). CONCLUSIONS: We demonstrated a final reattachment rate of 85.7% with a trend toward better vision following intervention for patients with RPRD. However, the final long-term vision may be poor due to the natural progression of retinitis pigmentosa-associated macular degeneration.

Poor mitochondrial health and systemic inflammation? Test of a classic hypothesis in the Baltimore Longitudinal Study of Aging.

Although a persistent inflammatory state has long been associated with aging and negative health outcomes, the underlying mechanisms remain unclear. Mitochondrial dysfunction has been proposed as a cause of inflammaging, but evidence of an association in humans is lacking. In this study, we analyzed the cross-sectional association between inflammatory biomarkers and mitochondrial oxidative capacity in skeletal muscle, assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy, in a population of 669 adults (mean age 67 years) from the Baltimore Longitudinal Study of Aging. We observed that participants with lower mitochondrial oxidative capacity exhibited hallmarks of inflammation, specifically markedly higher levels of interleukin-6 and C-reactive protein, as well as increased erythrocyte sedimentation rate when compared with participants with better oxidative capacity, independent of age and sex. We speculate that this association reflects the observation that products of damaged mitochondria, such as mitochondrial DNA, activate multiple pathways that lead to inflammation. Furthermore, excess production of oxidative species (ROS) by dysfunctional mitochondria could trigger inflammation either directly via NF-κB or through oxidative damage to proteins, lipids, and nucleic acids. Longitudinal studies are necessary to ascertain whether and through which mechanisms mitochondrial dysfunction activate inflammation or whether both these phenomena derive from a common root.

The Value of Outdoor Behavioral Healthcare for Adolescent Substance Users with Comorbid Conditions.

The damage inflicted on our society by mental health and substance use issues is reaching epidemic proportions with few signs of abating. One new and innovative strategy for addressing these comorbid issues has been the development of outdoor behavioral healthcare (OBH). This study compared the effectiveness of three post-acute adolescent substance use situations: OBH, treatment as usual (TAU), and no structured treatment (NST). The simulated target population was 13-17 years old with comorbid substance use and mental health issues. When costs were adjusted for actual completion rates of 94% in OBH, 37% in TAU, and $0 for NST, the actual treatment costs per person were $27 426 for OBH and $31 113 for TAU. OBH also had a cost-benefit ratio of 60.4% higher than TAU, an increased Quality in Life Years (QALY) life span, societal benefits of an additional $36 100, and 424% better treatment outcomes as measured by the Youth Outcome Questionnaire (YOQ) research instrument.

Descemet Membrane Endothelial Keratoplasty (DMEK) Graft Dislocation Into the Vitreous Cavity.

PURPOSE: To present our experience of Descemet stripping endothelial keratoplasty (DMEK) graft luxation into the vitreous cavity in 2 cases. METHODS: DMEK was performed in 2 patients with aphakic bullous keratopathy. The indications for keratoplasty were endothelial failure caused by chronic intermediate uveitis and glaucoma in 1 case and decompensated previous penetrating keratoplasty in the other. Both cases had enlarged pupils and had previously undergone pars plana vitrectomy. In both cases, the DMEK graft dislocated into the vitreous cavity during unfolding maneuvers and could not be retrieved during the same procedure. RESULTS: No signs of retinal detachment were observed during follow-up (6 months and 1 year). Although visualization of the graft was not possible on examination, B-scan confirmed the presence of the lenticule lying over the retina. One case underwent repeat DMEK, and 1 case underwent repeat penetrating keratoplasty. In 1 case, the graft was retrieved after a month and sent for histopathology. In both cases, corneal transparency and corrected visual acuity improved to full potential after the final procedure. Histopathology of the retrieved graft showed only endothelial cell loss and no fibrocellular proliferation. CONCLUSIONS: The risk of fibrous proliferation and retinal detachment after posterior dislocation of DMEK grafts may be less than in grafts including corneal stroma, but pars plana vitrectomy and retrieval of the dislocated corneal transplant are still indicated after revision corneal transplant surgery where visual symptoms or signs of fibrotic change around the dislocated graft are evident.

Age and Muscle Function Are More Closely Associated With Intracellular Magnesium, as Assessed by 31P Magnetic Resonance Spectroscopy, Than With Serum Magnesium.

Total serum magnesium is a common clinical measurement for assessing magnesium status; however, magnesium in blood represents less than 1% of the body's total magnesium content. We measured intramuscular ionized magnesium by phosphorus magnetic resonance spectroscopy (31P-MRS) and tested the hypothesis that this measure better correlates with skeletal muscle function and captures more closely the effect of aging than the traditional measure of total serum magnesium. Data were collected from 441 participants (age 24-98 years) in the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging that encompasses a broad age range. Results showed that intramuscular ionized magnesium was negatively associated with age (ß = -0.29, p < 0.001, R 2 = 0.08) and positively associated with knee-extension strength (ß = 0.31, p < 0.001, and R 2 = 0.1 in women; and ß = 0.2, p = 0.003, and R 2 = 0.04 in men), while total serum magnesium showed no association with age or strength (p = 0.27 and 0.1, respectively). Intramuscular ionized magnesium was significantly lower in women that in men (p < 0.001), perhaps due to chronic latent Mg deficiency in women that is not otherwise detected by serum magnesium levels. Based on these findings, we suggest that intramuscular ionized magnesium from 31P-MRS is a better clinical measure of magnesium status than total serum magnesium, and could be measured when muscle weakness of unidentified etiology is detected. It may also be used to monitor the effectiveness of oral magnesium interventions, including supplementation.

Moderate-to-Vigorous Physical Activity Is Associated With Higher Muscle Oxidative Capacity in Older Adults.

BACKGROUND: Age-related decline in muscle oxidative capacity reduces muscle function and physical performance, leading to disability and frailty. Whether age-related decline in oxidative capacity is modified by exercise and other lifestyle practices is unclear. Therefore, we tested the hypothesis that physical activity is associated with better oxidative capacity, independent of age. DESIGN: Cross-sectional study performed in the Baltimore Longitudinal Study of Aging, conducted by the Intramural Research Program (IRP) of the National Institute on Aging (NIA). SETTING: NIA IRP Clinical Research Unit, Baltimore, MD. PARTICIPANTS: Participants included 384 adults (54.7% women), aged 22 to 92 years, seen between 2013 and 2017. MEASUREMENTS: Muscle oxidative capacity was measured in vivo using phosphorous magnetic resonance spectroscopy. We determined the postexercise time constant (τPCr ; in seconds) for phosphocreatine (PCr) recovery, with lower values of τPCr, (ie, more rapid recovery of PCr levels after exercise) reflecting greater oxidative capacity. Time spent in moderate-to-vigorous physical activity (MVPA) was assessed using wearable accelerometers that participants wore 5.9 ± 0.9 consecutive days in the free-living environment. RESULTS: In linear regression models, higher τPCr was associated with older age (standardized ß = .39; P < .001) after adjusting for sex, race, height, and weight. After including MVPA as an independent variable, the standardized regression coefficient of age decreased by 40%, but remained associated with τPCr (ßage = .22; P < .001) and had a smaller standardized regression coefficient than MVPA (ßMVPA = -.33; P < .001). After adjusting for health status, education, and smoking history, the standardized regression coefficient for age decreased 12% (ßage = .20; P = .003), while the standardized coefficient for MVPA decreased only 3% (ßMVPA = -.32; P < .001). CONCLUSION: Study findings suggest that MVPA is strongly associated with muscle oxidative capacity, independent of age, providing mechanistic insights into the health benefits of exercise in older age. J Am Geriatr Soc 67:1695-1699, 2019.

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging.

The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (31 P-MRS) in 385 participants (256 women, 129 men), aged 24-97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), kPCr , was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography-tandem mass spectrometry. Adults in the highest quartile of kPCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine-learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of kPCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.

VITRECTOMY FOR PHACOANAPHYLACTIC GLAUCOMA SECONDARY TO POSTERIOR CAPSULAR RUPTURE IN AN ADULT WITH PERSISTENT HYPERPLASTIC PRIMARY VITREOUS.

PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental anomaly in which the normal regression of the primary vitreous and hyaloid vasculature does not occur. In the literature, there are a few cases of PHPV in adulthood. We report the novel presentation of phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with PHPV. We discuss the best management of this condition with a review of the literature on this topic. METHODS: Case report and literature review. RESULTS: Medical management was unsuccessful in this case and vitrectomy and fragmatome lensectomy improved vision from PL to counting fingers. CONCLUSION: This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome.